Although Parker acts like almost every other little kid, most days he
lives with joint pain, headaches, mouth ulcers, abdominal discomfort or
slight fevers. We give him ibuprofen or acetaminophen to keep
him comfortable but most days he just deals with his discomfort. On the
other hand, there are times when Parker will get severe swelling,
painful hives, excruciating headaches and high fevers (107.8 is the
highest so far, with tylenol in his system and laying on ice in the
hospital).

TRAPS (TNF Receptor-Associated Periodic Syndrome), formerly known as familial Hibernian fever, is characterized by long, dramatic, episodes of high fever; severe pain in the abdomen, chest, or joints; skin rash; and inflammation in or around the eyes. The age of onset varies from early childhood to adulthood, and the disease appears to affect men and women equally. The earliest cases of TRAPS were reported in individuals of Irish-Scottish descent, but the disease has since been found in nearly all ethnic groups.

TRAPS is caused by a genetic defect in a protein known as tumor necrosis factor receptor (TNFR). TNFR sits on the surface of cells and binds to tumor necrosis factor (TNF), a protein that causes inflammation. Mutant TNFR promotes inflammation without TNF. A person only needs one abnormal copy of the gene in order to get the disease. Episodes can be triggered by infection or stress. Although a definitive treatment for TRAPS has yet to be identified, drugs known as TNF inhibitors are sometimes successful in treating the disease.

General introductionRecent progresses in research have clearly shown that some rare fever diseases are caused by a genetic anomaly. In many of them, other members of the family can also suffer from recurrent fevers.

What does genetic anomaly mean?This means that a gene has been modified by an accident called a mutation. This mutation changes the function of the gene which gives wrong information to the body and results in the disease. In every cell, there are two copies of each gene. One copy is inherited from the mother and the other copy is inherited from the father. The mutation can bea) present in the parents. The inheritance is of 2 different types: -recessive: that means that both parents carry the mutation, on only one of their two genes. They are not ill because the disease occurs only if the two genes are affected. The risk for a child inheriting the mutation from each parent is one in four.-Dominant: that means that one mutation is enough to express the disease. In that case, one of the parents is ill, and the risk for transmission to the child is one in two.b)absent in the parents. The accident has occurred during the child’s conception. It is called de novo mutation. There is theoretically no risk for another child (no more than random), but the affected child’s offspring has the same risk of being affected as with the dominant mutation (i e one in two ).

WHAT IS IT?TRAPS is a dominantly inherited syndrome of recurrent high spiking fevers, usually of two to three weeks duration. The fever is typically accompanied by gastro-intestinal disturbances, painful red skin rashes, muscle pain and periorbital swelling. This disease is very newly recognized and understood.

How common is it?TRAPS is thought to be a rare disease with less than 100 confirmed cases, however, its true prevalence is currently unknown. It affects males and females equally and the onset seems to be during late childhood, or adulthood.The first cases were reported in patients from Irish-Scottish ancestry, however the disease has also been identified in other populations: French, Italians, Sephardic and Ashkenazi Jews, Armenians, Arabs and Kabylians from MaghrebThe seasons and climate have not been demonstrated to influence the course of the disease.

What are the causes of the disease?TRAPS is due to an inherited anomaly of a protein (Tumor Necrosis F Factor Receptor[TNFR]), which leads to an increase of the patient’s normal acute inflammatory response.An inflammatory hormone named tumor necrosis factor (TNF) overacts, because it is not controlled by the TNFR that normally binds to it and lowers the magnitude of inflammatory response.Infection, trauma or psychological stress may induce attacks.

Is it inherited?TRAPS has a dominant pattern of inheritance meaning that more than one case may be observed in a single family, every generation. The gradual reduction of family’s intermarriages (sibships) has lowered the possibility of this.

Why has my child got the disease? Can it be prevented?The child has inherited his disease from one of his parents that carries a TNFR gene mutations unless a de novo mutation has occurred.The person who carries the mutation may, or may not, exhibit the clinical symptoms of TRAPS. The disease cannot currently be prevented.

Is it contagious?TRAPS is not an infectious disease. Only genetically affected subjects develop the disease.

What are the main symptoms?The main symptoms are recurrent attacks of fever lasting typically two or three weeks, associated with chills and intense muscle pain involving the trunk and the upper limbs. The typical rash is red and painful, corresponding with underlying inflammation of the skin and muscle area.Most patients experience a sensation of deep cramping muscle pain at the onset of attacks that gradually increases in intensity and begins to migrate to other parts of the limbs, followed by the appearance of the rash. Diffuse abdominal pain with nausea and vomiting are common. Inflammation of the membrane covering the front of the eye (the conjunctiva), or periorbital swelling, is characteristic of TRAPS, although this symptom can be observed in other diseases.TRAPS may present somewhat differently with attacks of shorter or longer duration. Chest pain is also reported due to inflammation of the pleural (the membrane surrounding the lungs), or the pericardium (the membrane surrounding a joint) inflammation.Amyloidosis is the most severe complication of TRAPS, occurring in 14% of patients. It causes large amounts of proteins in the urine and progresses to renal failure.The relationship between amyloidosis and TRAPS probably relies on both chronic inflammation and genetic factors.

Is the disease the same in every child?TRAPS presentation varies from one patient to another in terms of the duration of each attack and the duration of symptom-free periods. The combination of the main symptoms is also variable. These differences may be explained, in part, by genetic factors.

How is it diagnosed?An expert physician will suspect TRAPS on the basis of clinical symptoms identified during a physical examination and from taking a family medical history.Several blood analyses are useful to detect inflammation during the attacks. The diagnosis is ascertained only by genetic analysis providing evidence of mutations. Differential diagnoses are other conditions presenting with recurrent fever especially Familial Mediterranean fever and HyperIgD syndrome.

What are the treatments?To date, no treatment exists to prevent or cure the disease. Non-specific anti-inflammatory agents help to relieve symptoms. High dose steroids are often effective but sustained usage leads to serious side effects. Specific TNF blockade has been shown to be an effective treatment in some patients when given at the beginning of an attack.

How long should treatments last for?The duration of treatment is limited to relieving acute symptoms, since no drug is effective for the prevention of fever attacks.

How long will the disease last for?TRAPS will manifests at repeated and irregular occasions throughout the life.

What is the long term prognosis (predicted outcome and course) of TRAPS?The prognosis is very variable, the worst prognosis affects only the minority of patients and these patients develop secondary amyloidosis. This risk is difficult to determine, because it depends on both genetic and environmental factors. Amyloidosis is a severe complication and frequently leads to renal failure.At the present time no one knows if this complication can be avoided.

Is it possible to recover completely?This possibility is currently unknown, but not excluded. Indeed, the genetic TNFR structural modification does not induce a functional defect in the bodies systems, making the discovery of a cure a perceivable possibility. Moreover, the eventual cessation of exposure to a potential triggering agent may induce sustained remission.